Abstract
Multiple Sclerosis (MS) is a neuro-degenerative and -inflammatory disease leading to physical and cognitive impairment, pathological fatigue and depression, and affecting patients' quality of life and employment status. The combination of inflammation, demyelination, and neurodegeneration leads to the emergence of MS lesions, reduced white and gray matter brain volumes, a reduced conduction velocity and microstructural changes in the so-called Normal Appearing White Matter (NAWM). Currently, there are very limited options to treat cognitive impairment and its origin is only poorly understood. Therefore, several studies have attempted to relate clinical scores with features calculated either using T1- and/or FLAIR weighted MR images or using neurophysiology. The aim of those studies is not only to provide an improved understanding of the processes that underlie the different symptoms, but also to develop a biomarker—sensitive to therapy induced change—that could be used to speed up therapeutic developments (e.g., cognitive training/drug discovery/…). Here, we provide an overview of studies that have established relationships between either neuro-anatomical or neurophysiological measures and cognitive outcome scores. We discuss different avenues that may help to improve the prediction of cognitive impairment, and how well we can expect them to predict cognitive scores.
Highlights
Cognitive impairment has been estimated to affect 1 out of every 2 multiple sclerosis (MS) patients (Rao et al, 1991) and affects different domains, most commonly information processing speed, working memory, long-term memory, attention, and executive functions (Langdon, 2011)
In contrast to physical disability, which can be monitored with the Expanded Disability Status Scale (EDSS, Kurtzke, 1983), cognitive impairment is difficult to assess as (1) neuropsychological evaluation demands time and (2) test results can be influenced by practice-effects, i.e., an improvement of test scores even when the disease is stable as the patients get practiced in the specific tests
Apart from general reductions/increases in diffusion parameters, several studies have found microstructural abnormalities in specific tracts like the fornix (Roosendaal et al, 2009; Kern et al, 2012), the cingulum (Mesaros et al, 2012), and the uncinate fasciculus (Fink et al, 2010). Several of these changes correlate with cognitive impairment: e.g., a reduced information processing speed was associated with reduced fractional anisotropy (FA) in the corpus callosum (Roosendaal et al, 2009) and higher FA in the fornix was related to better memory results (Kern et al, 2012)
Summary
Multiple Sclerosis (MS) is a neuro-degenerative and -inflammatory disease leading to physical and cognitive impairment, pathological fatigue and depression, and affecting patients’ quality of life and employment status. Several studies have attempted to relate clinical scores with features calculated either using T1- and/or FLAIR weighted MR images or using neurophysiology. The aim of those studies is to provide an improved understanding of the processes that underlie the different symptoms, and to develop a biomarker—sensitive to therapy induced change—that could be used to speed up therapeutic developments (e.g., cognitive training/drug discovery/...). We provide an overview of studies that have established relationships between either neuro-anatomical or neurophysiological measures and cognitive outcome scores.
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